BACKGROUND: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization. METHODS: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function. RESULTS: Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns). CONCLUSIONS: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.